Sequencing unlocks secrets of blood parasites

Researchers have sequenced the genomes of two species of flatworm that cause the tropical disease schistosomiasis, revealing
potential weaknesses that could be exploited by drug developers.

Schistosomiasis — also called bilharzia — is transmitted by water-borne snails, and affects more than 200 million people,
many of whom live in Africa. Infections are usually chronic, rather than fatal. There is currently only one drug, praziquantel,
in use against schistosomiasis and, although it is effective, scientists don't understand exactly how it works.

An international team led by Matthew Berriman at the Wellcome Trust Sanger Institute in Cambridge, UK, and Najib El-Sayed
at the University of Maryland in College Park has sequenced the genome of the parasite found throughout Africa (Schistosoma mansoni). The Asian strain (S. japonicum) was tackled by the Schistosoma japonicum Genome Sequencing and Functional Analysis Consortium. Both genomes are published
in Nature1,2.

Small fluke, big genome

The two genomes confirm theories about the flatworm's biology — for example, it depends on its host for fatty acids that
it can't make itself. But they also throw up some surprises. One is a new class of genes, thought to be involved in directing
the movements of proteins around the organism's cells, each of which is seen in a number of different forms. The researchers
think that this variation helps the parasite to hide from its host's immune system.

Another surprise is the size of the genomes. "This is a really big genome in terms of its overall length," says Berriman of
the African schistosome genome.

“If you've got a full genome, you've got a benchmark.”

Scott Lawton

Natural History Museum

Karl Hoffman, a schistosomiasis researcher at Aberystwyth University, UK, and his team are already using the genome information
to find targets for drugs and vaccines. Researchers are particularly interested, for example, in genes that are found in the
worm's genome but not in the human genome, so that the proteins they make could be targeted by drugs or vaccines. That includes
genes that, when knocked out, stop the female parasite producing eggs.

Berriman's group is also hunting for drug targets by looking for similarities. "We're now also looking for things that are
very similar to the host and for which drugs already exist," he says. "If we can persuade [drug companies] they may already
have things in their drug cabinet that could work, it could open up some new avenues." The drug cyclosporine, which is already
used in humans as an immune suppressant, is one possible candidate.

Going straight

The genomes could shed light on the early evolution of animals — specifically, the point at which animals started to develop
body plans that were straight rather than spherical like sea urchins. "Because schistosomes are flatworms, and flatworms occurred
very early in this process, they allow us to get much closer in time to that split," says Berriman.

Scott Lawton, a researcher at the Natural History Museum in London, is excited by the possible insights the genomes could
yield. In terms of discovering new genes, "it did fill in a lot of gaps", he says. It also shows which genes have moved around
in the genome — for example, the Hox genes, which control body pattern in animals, are clustered together in many animals, but in schistosomes they are scattered
around.

Although much of the S. mansoni data has been public for some time on the Wellcome Trust Sanger Institute website, assembling it all is still a milestone
that the community has been "looking forward to", says Hoffman.

"It doesn't matter what organism you work on and at what level," Lawton says. "If you've got a full genome, you've got a benchmark."